New Hope for Treating Osteosarcoma on the Horizon

Osteosarcoma is by far the most common form of bone cancer in dogs. About 75 to 85 percent of tumors occur on the legs, but they can develop in any bone. Middle-aged and older large- and giant-breed dogs are most commonly affected. The first sign is usually limping, which may start suddenly, or develop gradually, and is often accompanied by swelling at the tumor site. Within one to three months, the pain will be constant, and the tumor may cause the bone to fracture. Radiographs (x-rays) are usually all that is needed to confirm the diagnosis.

Because osteosarcoma has already metastasized (spread) in 90 to 95 percent of cases before it is discovered, treatment is aimed at prolonging life and improving quality of life, primarily by reducing pain. Surgery is the first line of treatment, including amputation of the limb, if practical. Surgery is rarely curative, but amputation leaves the dog pain-free to enjoy life for a time. Chemotherapy following surgical removal can prolong that time. Palliative therapies such as radiation are used for pain relief, especially when amputation is not an option. Drugs called bisphosphonates can be tried to inhibit bone destruction and relieve pain.

About half of dogs treated with surgery and chemotherapy will live for at least one year, and up to half of those will be alive after two years; occasionally, some dogs will be completely cured. Dogs treated only with amputation or palliative radiation therapy live on average about six months after diagnosis. The prognosis is not as good for dogs when elevated alkaline phosphatase, a liver enzyme, is found at time of diagnosis, and even worse for dogs when tumor cells are found in adjacent lymph nodes. Younger dogs tend to have more aggressive tumors and shorter survival times.

Now, new therapies are emerging that offer hope for prolonged life. Dr. Nichola Mason, an assistant professor at the University of Pennsylvania School of Veterinary Medicine, is conducting clinical trials using immunotherapy to treat dogs with osteosarcoma.

Immunotherapy is the term used for vaccines that stimulate the dog’s own immune system to destroy cancer cells. The vaccine Dr. Mason is using consists of genetically modified bacteria designed to express a tumor marker known as “Her2/neu,” which is also expressed in approximately 40 percent of canine osteosarcomas, as well as other types of cancers (including some forms of breast cancer in humans). If the vaccine triggers the immune system to attack the bacteria, the expectation is that it will then go on to seek out and eliminate any tumor cells remaining after chemotherapy.

The vaccine is given intravenously once a week for three weeks following amputation and chemotherapy. As of this writing, 12 dogs have been treated with the vaccine therapy. Side effects have been minimal, consisting primarily of short-term fever and sometimes nausea.

Of the first six dogs who received the vaccine, one dog who received a low dose of the vaccine had developed lung metastases, while the other five remained free of cancer a year later. Three of those dogs remained alive and cancer-free in November 2013, 500 or more days after initial therapy

A larger phase II clinical trial is now being planned at Penn and at collaborating sites including Colorado State University and the University of Florida. Dr. Mason hopes to include dogs unable to undergo amputation in future trials. She is also looking at the possibility of using the vaccine to prevent osteosarcoma in certain breeds at particularly high risk of the disease.

Palladia® (toceranib phosphate), a drug approved in 2009 for treatment of mast cell cancer, has also shown promise in treating osteosarcoma. Studies are currently underway at Colorado State University's Flint Animal Cancer Center to evaluate the effectiveness of toceranib for the treatment of dogs with osteosarcoma that has spread to the lung, and to evaluate markers in the blood that may help to determine which dogs will benefit most from toceranib treatment. The University of Pennsylvania's Veterinary Clinical Investigations Center is also conducting a trial to assess the effectiveness, safety and tolerability of Palladia in controlling or decreasing spread of the cancer and prolonging length of life in dogs with osteosarcoma following limb amputation.

Another clinical trial using targeted treatment for canine osteosarcoma is being conducted in Portland, Oregon. Doctors at The Keller Laboratory at Oregon Health and Science University have teamed with veterinarians at Oregon State University and Colorado State University to study osteosarcoma treatment in dogs, hoping it will lead to better treatment for children with this disease. Their goal is to develop personalized treatment by testing dozens of drugs on a tumor to determine which is most effective for that individual. Wally, the first dog treated in this manner, survived for 29 months after his treatment. Dr. Keller hopes to find more than 40 dogs with osteosarcoma to participate in this clinical trial.

More information:

Penn Vet (University of Pennsylvania School of Veterinary Medicine): Evaluation of a recombinant bacteria vaccine to treat bone cancer in dogs

Bone Marrow Transplants Promising for Treating Canine Lymphoma

Photo: Dr. Steven Suter performs a stem cell harvesting procedure on “Maverick the Weim,” the first dog with Acute Lymphoblastic Leukemia (AL) to undergo a bone marrow transplant. Maverick lived just three months after the procedure, but his case helped advance treatment strategies. His owners donated $10,000 and are fundraising to help buy a new leukapheresis machine at NCSU.

Exciting news regarding bone marrow transplants for dogs with lymphoma has recently emerged. North Carolina State University’s College of Veterinary Medicine in Raleigh is the first university in the world to open a canine clinical bone marrow transplant (BMT) unit. Dr. Steven Suter, assistant professor of veterinary oncology at NCSU, is about to perform his 30th transplant, all done over the past two years.

Lymphoma, also called lymphosarcoma, is one of the most common cancers to occur in dogs. While it used to be considered a disease of middle-aged and older dogs, those demographics have changed in the past 5 to 10 years, with more and more young dogs being diagnosed. Golden Retrievers have a particularly high risk for this type of cancer.

Lymphoma affects the lymph system, which is spread throughout the body, so surgery cannot be used to eradicate this form of cancer. Without treatment, most dogs die within two months of diagnosis. While chemotherapy can extend the life of dogs with lymphoma for up to two years, fewer than 2 percent of dogs are cured.

“The success rate for bone marrow transplants in people with lymphoma is 50 to 66 percent, and the hope is that dogs will respond similarly,” says Dr. Suter. Of the dogs who have received transplants at NC State in the past two years, 70 percent are still alive, but it’s still early days for many. Full results will not be known for a couple of years, but it is expected that even those dogs who are not completely cured will likely remain in remission for much longer than would have been the case without the transplant.

What the process entails

This is not actually a new technology, as bone marrow transplant protocols for people were originally developed in the 1970s from research done on dogs. The same leukophoresis machines used to harvest healthy stem cells from people can be used without modification for dogs.

“The dogs need to be in either complete remission or very close to complete remission to undergo the BMT procedure,” says Dr. Suter. “So, they all have to receive chemotherapy to get them to that point. Once in remission, they can have a BMT at any time afterward.”

The transplant procedure requires several days of preparation, starting with twice-daily injections of a drug called Neupogen, designed to drive healthy stem cells from the bone marrow into the bloodstream where they can be harvested. An ultra-low-fat diet is fed during this time, as lipids in the blood make stem cell extraction more difficult.

A week later, the dog is placed on a leukaphoresis machine that harvests stem cells from the blood. This process takes about six hours. The following day, the dog receives full body radiation to kill the cancer cells in his bone marrow. Immediately afterward, the stem cells that were harvested the day before are infused back into the bloodstream. The entire process is done under sedation or anesthesia and is painless for the dog.

Following the procedure, the dog is kept at the facility in an isolation ward for about two weeks to give the immune system time to recover as the stem cells start to regenerate. Vomiting and diarrhea due to the radiation are common during this time; drugs are given to combat these side effects. Antibiotics are given before and after the procedure to reduce the chances of bacteria entering the bloodstream and to help fight any infection while the immune system is suppressed. Blood transfusions from loss of platelets that are created by
the bone marrow.

For most dogs, no special care is needed after they return home. Hair loss and tiredness are the primary side effects at this time. Dogs will experience bouts of fatigue but should return to normal within four to six weeks.

Promising, not guaranteed

Not all dogs who receive a bone marrow transplant will be cured. While there is no way to know when a dog is completely cancer-free, most relapses so far have occurred in the first four months following the transplant. Dogs who make it beyond this point are more likely to be cured or remain cancer-free for two years or more.

The cost of a bone marrow transplant at NCSU runs from $13,000 to $17,000, averaging about $14,500. This includes everything except intensive ICU care, blood transfusions, and additional diagnostics that may be needed in some cases. There are additional monitoring costs after your dog returns home. Pet insurance may cover some of the cost of bone marrow transplants depending on the company and plan.

Stem cell extraction from bone marrow is more difficult with small dogs. “The smallest dog we’ve transplanted thus far was a 12.5-kg French bulldog (27.5 pounds),” says Dr. Suter. “We are getting ready to transplant an 11-kg (24 pounds) the lowest we can go is around 8 kg (or about 18-20 lbs).”

Dogs with serious health problems such as kidney or heart disease, or conditions that make infections more likely, such as diabetes or Cushing’s disease, do not qualify for the transplant procedure, as the risk would be too great.

Five private facilities in the U.S. are gearing up to offer bone marrow transplants for dogs. Eight transplants have been done by Edmund Sullivan, DVM, in Bellingham, Washington, beginning in 2004, but most of these clinics are just beginning to do or have not yet done their first procedures. There is some concern that it is too soon to be marketing bone marrow transplants so widely, before enough is known about the success rate and how to treat and prevent potential side effects. The five facilities are:

New Therapy for Brain Cancer

Breakthrough experimental treatment includes surgery, gene therapy, and a vaccine

News item written by Mary Straus, published in the Whole Dog Journal, September 2009.

The University of Minnesota College of Veterinary Medicine opened clinical trials in June 2009 for dogs with brain cancer. Any dog with a primary brain tumor (one that originates inside the brain) may be eligible. The program will cover almost all costs, including surgery and supportive care, for dogs enrolled in the trial.

Batman is a 10-year-old German Shepherd mix with an aggressive type of brain tumor – one that usually causes death within a month of diagnosis. In August 2008, Batman was the subject of what has developed as a breakthrough experimental treatment. One year later, Batman has no evidence of the disease – a response so impressive that the National Cancer Institute is funding further research for 50 dogs. If additional grants and donations come through, the number will be increased to more than 100 dogs. Without funding, treatment would cost between $10,000 and $20,000 per dog.

The new treatment consists of three phases. Surgery is done to remove as much of the tumor as possible. The site is then treated with a form of gene therapy designed to attract the dog’s immune system to destroy any remaining tumor cells. Finally, a vaccine is made from the dog’s own cancer cells and administered to prevent tumor recurrence.

Since Batman’s success, eight more dogs have been treated. In each case, their tumors shrank or disappeared.

This new type of treatment has the potential to be used for many other forms of cancer in both dogs and humans. Two comparative oncology specialists are working together: one is a veterinary surgeon, and the other heads up the university’s neurosurgery gene therapy program. Their hope is that the lessons learned from treating dogs will lead to better treatment options for humans with brain tumors as well.